Post-transplant lymphoproliferative disorders (PTLD) contribute significantly to the morbidity and mortality of these procedures. The current application seeks to address areas of clinical and laboratory investigation identified as important in a recent international consensus document. We plan a prospective multi-center clinical trial in which PTLD patients will be uniformly classified according to clinical and pathologic characteristics. Immunosuppressive medication will be reduced followed by observation. Patients who do not completely remit will enter a phase II trial to determine the safety and efficacy of the anti- CD20 antibody, rituximab. The accompanying tissue acquisition protocol will afford standardized diagnostic evaluation to include clonality, Epstein-Barr association and laboratory investigations. Mutations in the BCL-6 gene will be assessed by a single strand conformational polymorphisms and results will be correlated with clinical response to reduced immunosuppression and rituximab. Immunohistochemical analyses to determine the histogenesis of PTLD, proliferative fraction and bcl-2 expression are planned. Epstein-Barr viral genomes in the peripheral blood will be quantified using real-time PCR and the results will be correlated with response to reduced immunosuppression, rituximab and overall outcome.
In Aim 2 of this project gene expression patterns in PTLD will be evaluated using micro-array technology in conjunction with investigators in Project 5. We hypothesize that gene expression will improve our ability to predict the behavior of these heterogeneous disorders, for which routine pathologic analysis is inadequate. Differences in expression patterns may also predict response to our therapeutic interventions and provide clues to new treatments.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA034233-18
Application #
6446644
Study Section
Subcommittee E - Prevention &Control (NCI)
Project Start
2001-04-13
Project End
2002-03-31
Budget Start
Budget End
Support Year
18
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Myklebust, June H; Brody, Joshua; Kohrt, Holbrook E et al. (2017) Distinct patterns of B-cell receptor signaling in non-Hodgkin lymphomas identified by single-cell profiling. Blood 129:759-770
Anchang, Benedict; Hart, Tom D P; Bendall, Sean C et al. (2016) Visualization and cellular hierarchy inference of single-cell data using SPADE. Nat Protoc 11:1264-79
Sagiv-Barfi, Idit; Kohrt, Holbrook E; Burckhardt, Laura et al. (2015) Ibrutinib enhances the antitumor immune response induced by intratumoral injection of a TLR9 ligand in mouse lymphoma. Blood 125:2079-86
Behbehani, Gregory K; Samusik, Nikolay; Bjornson, Zach B et al. (2015) Mass Cytometric Functional Profiling of Acute Myeloid Leukemia Defines Cell-Cycle and Immunophenotypic Properties That Correlate with Known Responses to Therapy. Cancer Discov 5:988-1003
Levine, Jacob H; Simonds, Erin F; Bendall, Sean C et al. (2015) Data-Driven Phenotypic Dissection of AML Reveals Progenitor-like Cells that Correlate with Prognosis. Cell 162:184-97
Shroff, Emelyn H; Eberlin, Livia S; Dang, Vanessa M et al. (2015) MYC oncogene overexpression drives renal cell carcinoma in a mouse model through glutamine metabolism. Proc Natl Acad Sci U S A 112:6539-44
Spitzer, Matthew H; Gherardini, Pier Federico; Fragiadakis, Gabriela K et al. (2015) IMMUNOLOGY. An interactive reference framework for modeling a dynamic immune system. Science 349:1259425
Sagiv-Barfi, Idit; Kohrt, Holbrook E K; Czerwinski, Debra K et al. (2015) Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK. Proc Natl Acad Sci U S A 112:E966-72
Casey, Stephanie C; Vaccari, Monica; Al-Mulla, Fahd et al. (2015) The effect of environmental chemicals on the tumor microenvironment. Carcinogenesis 36 Suppl 1:S160-83
O'Gorman, William E; Hsieh, Elena W Y; Savig, Erica S et al. (2015) Single-cell systems-level analysis of human Toll-like receptor activation defines a chemokine signature in patients with systemic lupus erythematosus. J Allergy Clin Immunol 136:1326-36

Showing the most recent 10 out of 523 publications